1,721,560 research outputs found
Molecular epidemiology and population genomics of Plasmodium knowlesi.
Full text linkMolecular epidemiology has been central to uncovering P. knowlesi as an important cause of human malaria in Southeast Asia, and to understanding the complex nature of this zoonosis. Species-specific parasite detection and characterization of sequences were vital to show that P. knowlesi was distinct from the human parasite species that had been presumed to cause all malaria. With established sensitive and specific molecular detection tools, surveys subsequently indicated the distribution of P. knowlesi infections in humans, wild primate reservoir host species, and mosquito vector species. The importance of studying P. knowlesi genetic polymorphism was indicated initially by analysing a few nuclear gene loci as well as the mitochondrial genome, and subsequently by multi-locus microsatellite analyses and whole-genome sequencing. Different human infections generally have unrelated P. knowlesi genotypes, acquired from the diverse local parasite reservoirs in macaques. However, individual human infections are usually less genetically complex than those of wild macaques which experience more frequent superinfection with different P. knowlesi genotypes. Multi-locus analyses have revealed deep population subdivisions within P. knowlesi, which are structured both geographically and in relation to different macaque reservoir host species. Simplified genotypic discrimination assays now enable efficient large-scale surveillance of the sympatric P. knowlesi subpopulations within Malaysian Borneo. The whole-genome sequence analyses have also identified loci under recent positive natural selection in the P. knowlesi genome, with evidence that different loci are affected in different populations. These provide a foundation to understand recent adaptation of the zoonotic parasite populations, and to track and interpret future changes as they emerge
Chris Drakeley - combatting malaria
No full textDr Chris Drakeley, from the London School of Hygiene & Tropical Medicine's Malaria Centre, discusses malaria, the problems we face, and ongoing research at the School to treat and prevent the disease
Assessment of exposure, infection and risk for malaria in Afghan refugee camps in Khyber Pakhtunkhwa (KP), Pakistan
Full text linkNorthern Pakistan, Khyber Pakhtunkhwa (KP) is low malaria endemic area characterised by seasonal transmission with predominantly vivax malaria. Migration of high number of Afghan Refugees in 1978 into KP led to concerns for an increase in malaria, as the malaria incidence in this group was reportedly high compared to the local Pakistani population. Considerable progress has been made in controlling malaria through operational research in the camps where the Afghan refugees reside. However, this process requires effective, repeatable active surveillance tools for monitoring malaria control as availability of accurate data is the major challenge at present.
The aim of this PhD project was to generate current information on malaria infection rates through parasite prevalence and malaria exposure using antimalarial antibody responses.The project also investigated the risk factors of malaria and heterogeneity in the geographic distribution of malaria in the camps by using GIS data with serological responses and parasite prevalence data. As an ancillary objective the project aimed to determine the prevalence of G6PO deficiency in the study population.
A cross-sectional survey was conducted in five Afghan refugee camps of KP between June and September in 2010. Blood samples were obtained on filter paper from 2526 individuals and tested by rapid diagnostic test, paraSite species specific PCR and ElISA for antibody responses to Plasmodium vivax and Plasmodium falciparum. A questionnaire was administered to collect household and individual based information to determine the potential risk factors of malaria.
Heterogeneity in malaria was observed between the studied camps based on seroprevalence, which ranged from 17%-45% for P. vivax and 3% to 11% for P. falciparum. Variation in P. vivax infection prevalence was also detected between the camps, which ranged from 0.4-9% (ROT) and 5-15% (peR). Variation in the distribution of malaria was also found within the camp using spatial/GIS data with clear foci of infection identified in 4 of 5 camps. The results showed that as expected parasite based prevalence measures (ROT and peR) are significantly lower than serological measure of exposure. P. falciparum infection prevalence (ROT and PCR) and seroprevalence was found to be extremely low with P. vivax infections predominant. Age seroprevalence changes were more pronounced for P. vivax than P. falciparum and seroconversion rate was strongly associated with parasite rate.
Increasing age .and poorly built houses were associated with increasing risk, while staying in the same camp for the last 6 months and using measures to reducing vector biting such as repellents repellent, coils or insecticide spraying were associated with reduce risk of falciparum malaria. The risk of vivax malaria was observed to increase with increasing age, sharing house with cattle and having fever within 24 hours or two weeks and a reduction in the risk was seen in the individuals who reported use of Insecticide treated Bed Nets (ITN) night prior to surveyor used self protection measures from vector. The 563C-T polymorphism of G6PD gene was observed in only 2 unrelated individuals out of 505 individuals tested (O.4%). In conclusion, both parasitological and serological measures were able to detect spatial variation in infection and exposure to malaria at the micro epidemiological level within the camp. This data will help to provide beneficial and up-to-date information to manage control activities in the study area
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
The Human Infectious Reservoir of Falciparum Malaria
Full text linkMalaria control strategies are often targeted at individuals who suffer most morbidity, not at those driving transmission. This is in part due to our limited understanding, described in Chapter 1, of the human infectious reservoir of falciparum malaria – i.e. individuals responsible for human-to-mosquito transmission of Plasmodium falciparum parasites in endemic areas. This work, whose objectives are listed in Chapter 2, assessed the prevalence of infectiousness in naturally exposed human populations during dry and wet seasons. Exposure to Anopheles mosquitoes, a measure of transmission opportunities, was also quantified; and to determine the value of infectiousness-reducing interventions, the use of primaquine to block transmission from infectious individuals was investigated.
Experimental infections of mosquitoes were performed to determine malaria infectivity of randomly selected individuals in two villages in Burkina Faso. Molecular assays were used to quantify parasite, including gametocyte, densities. Less than 10% of the population was infectious to mosquitoes. These results are presented in a manuscript that included data from other study sites (Chapter 3).
To assess exposure to malaria vectors, bloodfed mosquitoes were collected indoors in one of the study villages in Burkina Faso. A multiplex PCR assay targeting nine human microsatellites and a gender-specific marker was used to identify the human sources of mosquito blood meals. Although there was substantial variation in the number of mosquito bites each individual received (Chapter 4), on average adults received more mosquito bites than children. This suggests that, despite their lower infectiousness, adults are major contributors to malaria transmission in endemic areas.
An efficacy trial of single low dose primaquine was performed in Burkina Faso and pre- and post-treatment infectiousness were quantified by mosquito feeding experiments to assess primaquine’s infectiousness-reducing activity (Chapter 5). Individuals receiving primaquine cleared gametocytes faster than individuals who received artemether-lumefantrine alone. Feeding assays, however, suggest that artemether-lumefantrine blocks most parasite transmission after treatment administration.
In Chapter 6, these findings, and how they can inform future control strategies, are discussed
Operational applications of serology for malaria surveillance in different transmission settings in Indonesia
Full text linkSerological surveillance involves the detection of Plasmodium species-specific antibodies as biomarkers for monitoring recent and historical malaria transmission dynamics at population-level. These methods are particularly useful in low transmission settings where standard surveillance such as parasitological and entomological approaches are inefficient. This thesis explores the use of serological surveillance to estimate the magnitude and heterogeneity of malaria transmission using different sampling strategies, mapping techniques and serological assays in three areas of differing endemicity in Indonesia. Findings suggest that: 1) Analysis of community-based serological data can confirm the discontinuation of transmission and be used to identify high-risk areas where malaria is most likely to be reintroduced, 2) Mobile technology-based participatory mapping approaches can be used to quickly obtain spatial residential information for individuals presenting at health facilities in resource poor areas where formal addresses are typically not used and internet connectivity is limited, 3) the combination of facility-based sampling, multiplex serological assays and participatory mapping can be used as an additional surveillance method to better identify and target areas still receptive to malaria in very low transmission area conducting elimination, 4) seropositivity to Etramp5.Ag1 is sensitive and specific in predicting Plasmodium falciparum PCR positivity in children in a high transmission setting, suggesting its potential use as a marker of recent exposure in elimination setting. In conclusion, this thesis demonstrates the various applications of serological surveillance at different levels of malaria endemicity. Further implementation research is needed to enable the integration of these methods to the existing surveillance systems
Operational Strategies for the Identification and Targeting of Hotspots of Malaria Transmission
Full text linkHeterogeneous
malaria
exposure
may
result
in
distinct
clusters
of
higher
malaria
burden,
or
hotspots,
across
space
and
time.
Targeting
control
programs
to
these
areas
may
be
highly
efficient,
however,
operationally
attractive
approaches
for
identifying
hotspots
are
needed
for
any
such
program
to
be
sustained
by
local
malaria
control
programs.
The
principal
aim
of
this
project
was
to
investigate
the
ability
of
convenient
sampling
to
identify
hotspots
of
malaria
transmission
in
a
low
endemic
transmission
setting
in
the
western
Kenyan
highlands:
1)
The
boundaries
of
hotspots,
and
associated
uncertainties,
was
determined
using
a
large
community
survey;
2)
The
value
of
convenience
sampling
to
estimate
transmission
in
the
community
was
assessed
using
cross-‐sectional
surveys
of
4964
children
in
46
government
primary
schools
and
3042
individuals
in
five
rural-‐health
facilities;
3)
The
value
of
compound-‐level
screening
of
sentinel
age
groups
that
are
likely
to
have
patent
level
infections
was
determined
and;
4)
The
potential
use
for
convenience
sampling
in
hotspot
targeted
approaches
was
assessed
using
spatial
information
on
residences
collected
during
the
school
and
health-‐facility
surveys.
The
community-‐based
approach
was
able
to
detect
77%
of
the
parasite
infections
in
selected
hotspots
of
malaria
exposure
using
field-‐based
tools
in
sentinel
age
groups.
Both
convenience-‐sampling
approaches
tested
produced
similar
estimates
of
malaria
transmission
to
the
community
when
restricted
to
those
residing
in
the
same
catchment
areas
and
those
testing
positive
for
malaria
were
more
likely
to
reside
in
a
hotspot.
The
findings
suggest
that
operationally
attractive
approaches
provide
reliable
information
on
malaria
transmission
and
may\ud
play
an
important
role
in
targeted
malaria
control
strategies.
Future
research
on
ascertaining
what
coverage
of
the
hotspot
is
needed
to
see
sustainable
reductions
in
transmission
would
provide
a
threshold
with
which
to
gauge
the
utility
of
this
strategy
Novel approaches to sex-ratio studies in plasmodium falciparum
Full text linkMalaria parasites are able to alter the number of male and female gametocytes produced, thereby changing the sex ratio of the reproductive stages. Alteration of the sex ratio has been suggested to increase the reproductive oputput under different conditions, thereby maximizing the transmission success and influencing the epidemiology of this disease.
The only existing method for quantifying sex ratios of P. Jalciparum is based on the visual identification of male and female gametocytes by light microscopy. However, this method is limited, as it only allows studying microscopically detectable gametocyte densities found in natural infections and parasites at sub-microscopic levels are not accounted for. A new and more accurate method for estimating sex ratios of P. Jalciparum, which includes large sample sizes obtained by magnetic purification, is described here. In this study light microscopy, immunofluorescent antibody detection (IFA) and quantitative Real-Time PCR (qRT-PCR) were used to estimate sex ratios in P. Jalciparum.
The qRT-PCR assay allowed measurement of mRNA expression levels for sexspecific and sexual stage proteins in a multiplex analysis. The female specific protein Pfg377 (PFL2405c) and the putative male specific protein Alpha-tubulin II (PFD1050w) were used to quantify either female or male gametocytes, with Pfs16 (pFD0310w) and Pfs25 (PFlO_0303) serving to quantify the total number of gametocytes present. Results suggest that Alpha-tubulin II is not in fact a male specific protein, whereas Pfg377 was found to be only present in female gametocytes. Different patterns of gene expression during gametocytogenesis have been identified for the four key sexual stage genes in a multiplex assay. Relative expression data of Pfg377 versus Pfs 16 or Pfs25 reveal that the quantification of sex ratios from small volumes of gametocyte-positive blood is possible, and should be applicable for using finger-prick peripheral blood samples from gametocyte carriers
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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